Clinical application of
treprostinil in
pulmonary arterial hypertension is hampered by adverse effects caused by its high dosing frequency. The objective of this investigation was to Formulate an adhesive-type
transdermal patch of
treprostinil and evaluate it both in vitro and in vivo. A 32-factorial design was utilized to optimize the selected independent variables (X1:
drug amount, X2: enhancer concentration) on the response variables (Y1: drug release, Y2: transdermal flux). The optimized patch was evaluated for various
pharmaceutical properties, skin irritation, and pharmacokinetics in rats. Optimization results signify considerable influence (p < 0.0001) of X1 on both Y1 and Y2, as compared to X2. The optimized patch possesses higher
drug content (>95%), suitable surface morphology, and an absence of
drug crystallization. FTIR analysis revealed compatibility of the
drug with
excipients, whereas DSC thermograms indicate that the
drug exists as amorphous in the patch. The adhesive properties of the prepared patch confirm adequate adhesion and painless removal, while the skin irritation study confirms its safety. A steady drug release via Fickian diffusion and greater transdermal delivery (~23.26 µg/cm2/h) substantiate the potential of the optimized patch. Transdermal
therapy resulted in higher
treprostinil absorption (p < 0.0001) and relative bioavailability (237%) when compared to
oral administration. Overall, the results indicate that the developed
drug in the adhesive patch can effectively deliver
treprostinil through the skin and could be a promising treatment option for
pulmonary arterial hypertension.